The innate immunity of the vaginal tract provides first-line defense from abnormal microorganisms or overgrowth of common organisms, such as Candida species or Gardnerella vaginalis. It is unclear from the current available literature whether the rate of vaginal infection increases or decreases in frequency during pregnancy when compared to the non-pregnant state, but this may be predicted by shifts in vaginal innate immunity. Vaginal infections are important players in HIV disease, potentially increasing the risk of viral transmission. In addition, these infections may activate inflammatory markers in the reproductive tract and increase the risk of premature delivery or other negative pregnancy outcomes. The vaginal innate immune system has not been well characterized in pregnant women, or in women with HIV infection. The study of how this system changes in pregnancy and HIV infection will provide essential knowledge for further study of vaginal mucosal protection.